Absence of Regulatory T Cells Causes Phenotypic and Functional Switch in Murine Peritoneal Macrophages.

Tissue macrophages are important components of tissue homeostasis and inflammatory pathologies. In the peritoneal cavity, resident macrophages interact with a variety of immune cells and can exhibit broad range of phenotypes and functions. Forkhead-box-P3 (FOXP3) regulatory T cells (Tregs) play an indispensable role in maintaining immunological tolerance, yet whether, and how the pathological condition that results from the lack of functional Tregs affects peritoneal macrophages (PM) is largely unknown.

Vitiligo after alemtuzumab treatment: Secondary autoimmunity is not all about B cells.

Objective: To report 3 patients with relapsing-remitting multiple sclerosis (RRMS) showing vitiligo after treatment with alemtuzumab.

Methods: Retrospective case series including flow cytometric analyses and T-cell receptor (TCR) sequencing of peripheral blood mononuclear cells.

Results: We describe 3 cases of alemtuzumab-treated patients with RRMS developing vitiligo 52, 18, and 14 months after alemtuzumab initiation.

Polarity-specific modulation of pain processing by transcranial direct current stimulation - a blinded longitudinal fMRI study.

Background: To enrich the hitherto insufficient understanding regarding the mechanisms of action of transcranial direct current stimulation (tDCS) in pain disorders, we investigated its modulating effects on cerebral pain processing using functional magnetic resonance imaging (fMRI).

Methods: Thirteen right-handed healthy participants received 20 min of 1.5 mA tDCS applied over the primary motor cortex thrice and under three different stimulation pattern (1.

Postacute Delivery of GABA α5 Antagonist Promotes Postischemic Neurological Recovery and Peri-infarct Brain Remodeling.

Background and Purpose- Poststroke, neuronal excitability is tonically reduced in peri-infarct tissue via inhibitory influences of extrasynaptic GABA receptors. We hypothesized that GABA α5 blockade by the competitive antagonist S44819 enhances postischemic neurological recovery, brain remodeling, and neuroplasticity. Methods- In an explorative study followed by a confirmation study, male C57Bl6/j mice were exposed to transient intraluminal middle cerebral artery occlusion.

Apheresis therapies for NMOSD attacks: A retrospective study of 207 therapeutic interventions.

Objective: To analyze whether 1 of the 2 apheresis techniques, therapeutic plasma exchange (PE) or immunoadsorption (IA), is superior in treating neuromyelitis optica spectrum disorder (NMOSD) attacks and to identify predictive factors for complete remission (CR).

Methods: This retrospective cohort study was based on the registry of the German Neuromyelitis Optica Study Group, a nationwide network established in 2008. It recruited patients with neuromyelitis optica diagnosed according to the 2006 Wingerchuk criteria or with aquaporin-4 (AQP4-ab)-antibody-seropositive NMOSD treated at 6 regional hospitals and 16 tertiary referral centers until March 2013.

Laboratory biomarkers of delayed cerebral ischemia after subarachnoid hemorrhage: a systematic review.

Delayed cerebral ischemia (DCI) is a severe complication of subarachnoid hemorrhage (SAH). Clinical and radiographic features of SAH may be helpful in identification of individuals prone to DCI. The aim of this systematic review was to analyze the present evidence on predictive value of blood and cerebrospinal fluid (CSF) biomarkers of DCI after SAH.

Feasibility and safety of intrathecal treatment with nusinersen in adult patients with spinal muscular atrophy.

Background: Nusinersen is an intrathecally administered antisense oligonucleotide (ASO) and the first approved drug for the treatment of spinal muscular atrophy (SMA). However, progressive neuromyopathic scoliosis and the presence of spondylodesis can impede lumbar punctures in SMA patients. Our aim was to assess the feasibility and safety of the treatment in adults with SMA.

Role of polymorphonuclear neutrophils in the reperfused ischemic brain: insights from cell-type-specific immunodepletion and fluorescence microscopy studies.

Polymorphonuclear neutrophil granulocytes (PMNs) are part of the early post-ischemic immune response that orchestrates the removal of infarcted brain tissue. PMNs contribute to secondary brain injury in experimental stroke models. In human patients, high PMN-to-lymphocyte ratios in peripheral blood are predictive of poor stroke outcome.

Symptomatology and symptomatic treatment in multiple sclerosis: Results from a nationwide MS registry.

Background: Multiple sclerosis (MS) is a neuroinflammatory and neurodegenerative disease. Over time, symptoms accumulate leading to increased disability of patients.

Objective: The objective of this article is to analyze the prevalence of symptoms and symptomatic treatment patterns in a nationwide MS registry.

Automated ASPECT rating: comparison between the Frontier ASPECT Score software and the Brainomix software.

Purpose: Computer-aided diagnosis (CAD) appears promising in early ischemic change detection computed tomography (CT). This study aimed to compare the performance of two new CAD systems (Frontier ASPECTS Prototype and Brainomix) with two experienced readers in selected patients with suspected acute ischemic stroke.

Methods: Retrospectively, non-contrast brain CTs of 150 patients suspected for acute middle cerebral artery ischemia were analyzed with respect to ASPECTS first separately, than in consensus by two senior radiologists, and by use of Frontier and Brainomix.

CIDP, myasthenia gravis, and membranous glomerulonephritis - three autoimmune disorders in one patient: a case report.

Background: We present a patient fulfilling the electrophysiological criteria for definite chronic inflammatory demyelinating polyneuropathy (CIDP), antibody-positive myasthenia gravis (MG), and membranous glomerulonephritis (MGN) confirmed by biopsy. To our knowledge, this is the first case of the concomitant appearance of these three autoimmune diseases in a single patient.

Case Representation: A 42-year-old Caucasian male presented with rapidly progressive gait disturbance, distal weakness of the lower extremities, ascending hypoesthesia, impaired fine motor skills, and beginning cranial nerve palsy showing dysarthrophonia, facial paralysis, and eye movement abnormalities and was diagnosed as rapid onset (atypical) CIDP.

The Coagulation Factors Fibrinogen, Thrombin, and Factor XII in Inflammatory Disorders-A Systematic Review.

Background: The interaction of coagulation factors has been shown to go beyond their traditional roles in hemostasis and to affect the development of inflammatory diseases. Key molecular players, such as fibrinogen, thrombin, or factor XII have been mechanistically and epidemiologically linked to inflammatory disorders like multiple sclerosis (MS), rheumatoid arthritis (RA), and colitis.

Objectives: To systematically review the evidence for a role of coagulation factors, especially factor XII, fibrinogen, and thrombin in inflammatory disorders like MS, RA, and bowel disorders.

Anti-CD52 antibody treatment depletes B cell aggregates in the central nervous system in a mouse model of multiple sclerosis.

Background: Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system (CNS) for which several new treatment options were recently introduced. Among them is the monoclonal anti-CD52 antibody alemtuzumab that depletes mainly B cells and T cells in the immune periphery. Considering the ongoing controversy about the involvement of B cells and in particular the formation of B cell aggregates in the brains of progressive MS patients, an in-depth understanding of the effects of anti-CD52 antibody treatment on the B cell compartment in the CNS itself is desirable.

Topological remodeling of cortical perineuronal nets in focal cerebral ischemia and mild hypoperfusion.

Despite the crucial role of perineuronal nets (PNNs) in neural plasticity and neurological disorders, their ultrastructural organization remains largely unresolved. We have developed a novel approach combining superresolution structured illumination microscopy (SR-SIM) and mathematical reconstruction that allows for quantitative analysis of PNN topology. Since perineuronal matrix is capable to restrict neural plasticity but at the same time is necessary to maintain synapses, we hypothesized that a beneficial post stroke recovery requires a reversible loosening of PNNs.

Trapped in the epineurium: early entry into the endoneurium is restricted to neuritogenic T cells in experimental autoimmune neuritis.

Background: Autoimmune polyneuropathies are acquired inflammatory disorders of the peripheral nervous system (PNS) characterized by inflammation, demyelination, and axonal degeneration. Although the pathogenesis has not been fully elucidated, T cells recognizing self-antigens are believed to initiate inflammation in a subgroup of patients. However, the route and time of T cell entry into the PNS have not yet been described in detail.

Detection of early infarction signs with machine learning-based diagnosis by means of the Alberta Stroke Program Early CT score (ASPECTS) in the clinical routine.

Purpose: New software solutions emerged to support radiologists in image interpretation in acute ischemic stroke. This study aimed to validate the performance of computer-aided assessment of the Alberta Stroke Program Early CT score (ASPECTS) for detecting signs of early infarction.

Methods: ASPECT scores were assessed in 119 CT scans of patients with acute middle cerebral artery ischemia.

Functional Relevance of the Anaphylatoxin Receptor C3aR for Platelet Function and Arterial Thrombus Formation Marks an Intersection Point Between Innate Immunity and Thrombosis.

Background: Platelets have distinct roles in the vascular system in that they are the major mediator of thrombosis, critical for restoration of tissue integrity, and players in vascular inflammatory conditions. In close spatiotemporal proximity, the complement system acts as the first line of defense against invading microorganisms and is a key mediator of inflammation. Whereas the fluid phase cross-talk between the complement and coagulation systems is well appreciated, the understanding of the pathophysiological implications of such interactions is still scant.

Immunotherapy of experimental and human stroke with agents approved for multiple sclerosis: a systematic review.

Background: 'Thromboinflammation' describes a novel concept in stroke pathophysiology that has opened up the possibility of immunotherapeutic approaches which could become promising strategies for targeted stroke therapies in the future.

Methods: We reviewed current evidence for agents approved for multiple sclerosis in preclinical and clinical stroke studies. A systematic review was performed in accordance with the PRISMA statement, searching MEDLINE, the Cochrane Central Register of Controlled Trials, and reference lists of articles published until 16 October 2017.

Protective potential of dimethyl fumarate in a mouse model of thalamocortical demyelination.

Alterations in cortical cellular organization, network functionality, as well as cognitive and locomotor deficits were recently suggested to be pathological hallmarks in multiple sclerosis and corresponding animal models as they might occur following demyelination. To investigate functional changes following demyelination in a well-defined, topographically organized neuronal network, in vitro and in vivo, we focused on the primary auditory cortex (A1) of mice in the cuprizone model of general de- and remyelination. Following myelin loss in this model system, the spatiotemporal propagation of incoming stimuli in A1 was altered and the hierarchical activation of supra- and infragranular cortical layers was lost suggesting a profound effect exerted on neuronal network level.

Implications of polymorphonuclear neutrophils for ischemic stroke and intracerebral hemorrhage: Predictive value, pathophysiological consequences and utility as therapeutic target.

Polymorphonuclear neutrophil granulocytes (PMN) orchestrate the removal of cell debris in ischemic stroke and intracerebral hemorrhage. In both pathologies, high neutrophil to lymphocyte ratios in peripheral blood are predictive of poor outcome in human stroke patients. Following earlier studies indicating that the cerebral microvasculature forms an efficient barrier that impedes neutrophil brain entry, intravital microscopy and immunohistochemistry in the meantime unequivocally revealed the accumulation of PMN in the ischemic and hemorrhagic brain parenchyma.

Alemtuzumab as rescue therapy in a cohort of 50 relapsing-remitting MS patients with breakthrough disease on fingolimod: a multi-center observational study.

Background: Relapsing-remitting multiple sclerosis (RRMS) requires efficient immunomodulatory treatment to reach "no evidence of disease activity" status at best. Alemtuzumab and fingolimod have proved to be efficient options in RRMS with active disease course. Yet, side effects and break-through disease may limit long-time treatment and necessitate switch of medication.

Oxaliplatin Modulates the Characteristics of Voltage-Gated Calcium Channels and Action Potentials in Small Dorsal Root Ganglion Neurons of Rats.

Oxaliplatin is important for treating colorectal cancer. Although oxaliplatin is highly effective, it has severe side effects, of which neurotoxicity in dorsal root ganglion (DRG) neurons is one of the most common. The key mechanisms of this neurotoxicity are still controversial.

Advances in Multiple Sclerosis 2017.

Multiple sclerosis (MS) is one of the most emerging fields in neurology[...